Some Epidemiological Aspects of Cutaneous Leishmaniasis in a New Focus, Central Iran

Following the epidemic of cutaneous leishmaniasis in Khatam County, Yazd Province, this study was carried out to determine vector, and animal reservoir host(s) and investigate the human infection during 2005-2006. Four rural districts where the disease had higher prevalence were selected. Sticky paper traps were used to collect sand flies during April to November, biweekly. Meanwhile rodents were captured using Sherman traps from August to November. Households and primary schools were visited and examined for human infection in February 2006. The parasite was detected by RAPD-PCR method. The rate of ulcers and scars among the inhabitants was 4.8% and 9.8%, respectively. Three rodent species were captured during the study:Meriones libycus, Rhombomys opimus, andTatera indica. Six sand fly species were also collected and identified; among themPhlebotomus papatasihad the highest frequency.Leishmania majorwas detected as the agent of the disease in the area. It was detected fromR. opimusand native people.

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Transgenic Expression of CXCR3 on T Cells Enhances Susceptibility to Cutaneous Leishmania major Infection by Inhibiting Monocyte Maturation and Promoting a Th2 Response

Infection and Immunity ◽

10.1128/iai.02540-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 67-76 ◽

Cited By ~ 5

Author(s):

Steve Oghumu ◽

James C. Stock ◽

Sanjay Varikuti ◽

Ran Dong ◽

Cesar Terrazas ◽

...

Keyword(s):

T Cells ◽

Cutaneous Leishmaniasis ◽

Leishmania Major ◽

Critical Role ◽

Sand Fly ◽

Interleukin 4 ◽

Th2 Response ◽

Content Type ◽

Transgenic Expression ◽

Inflammatory Monocytes

Cutaneous leishmaniasis, caused mainly byLeishmania major, an obligate intracellular parasite, is a disfiguring disease characterized by large skin lesions and is transmitted by a sand fly vector. We previously showed that the chemokine receptor CXCR3 plays a critical role in mediating resistance to cutaneous leishmaniasis caused byLeishmania major. Furthermore, T cells fromL. major-susceptible BALB/c but notL. major-resistant C57BL/6 mice fail to efficiently upregulate CXCR3 upon activation. We therefore examined whether transgenic expression of CXCR3 on T cells would enhance resistance toL. majorinfection in susceptible BALB/c mice. We generated BALB/c and C57BL/6 transgenic mice, which constitutively overexpressed CXCR3 under a CD2 promoter, and then examined the outcomes withL. majorinfection. Contrary to our hypothesis, transgenic expression of CXCR3 (CXCR3Tg) on T cells of BALB/c mice resulted in increased lesion sizes and parasite burdens compared to wild-type (WT) littermates afterL. majorinfection. Restimulated lymph node cells fromL. major-infected BALB/c-CXCR3Tgmice produced more interleukin-4 (IL-4) and IL-10 and less gamma interferon (IFN-γ). Cells in draining lymph nodes from BALB/c-CXCR3Tgmice showed enhanced Th2 and reduced Th1 cell accumulation associated with increased neutrophils and inflammatory monocytes. However, monocytes displayed an immature phenotype which correlated with increased parasite burdens. Interestingly, transgenic expression of CXCR3 on T cells did not impact the outcome ofL. majorinfection in C57BL/6 mice, which mounted a predominantly Th1 response and spontaneously resolved their infection similar to WT littermates. Our findings demonstrate that transgenic expression of CXCR3 on T cells increases susceptibility of BALB/c mice toL. major.

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Molecular characterization of Leishmania tropica and Leishmania major from stray dogs and patients in Saudi Arabia

10.21203/rs.2.22961/v2 ◽

2020 ◽

Author(s):

Abdullah D Alanazi ◽

Abdulazi S Alouffi S Alouffi ◽

Mohamed S Alyousif S Alyousif ◽

Abdulsadah A Rahi ◽

Magda A Ali ◽

...

Keyword(s):

Saudi Arabia ◽

Cutaneous Leishmaniasis ◽

Nested Pcr ◽

Leishmania Major ◽

Sand Fly ◽

Human Populations ◽

Leishmania Tropica ◽

Stray Dogs ◽

Wild Canids ◽

Control And Prevention

Abstract Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when occurring in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. Methods: To determine the prevalence and to identify the species of Leishmania that infects humans and stray dogs in Riyadh and Al-Qassim (Saudi Arabia), 311 stray dogs and 27 human patients, suspected for Leishmania, were examined for CL by a nested PCR (nPCR).Results: Nested PCR (nPCR) detected seven patients (25.9%) positive for cutaneous leishmaniasis. Five patients from Riyadh were infected by L. major and two from Al-Qassim by L. tropica. In addition, five dogs (1.6%) were infected by L. tropica. Conclusions: This is one of the first molecular studies of leishmaniasis from Saudi Arabia. The relationship between the sand fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and further epidemiological investigations of domestic and wild canids infected with L. major and L. tropica are needed towards a control and prevention of the infection in canine and human populations.

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Epidemiological study in a new focus of cutaneous leishmaniasis in the Islamic Republic of Iran

Eastern Mediterranean Health Journal ◽

10.26719/2003.9.4.816 ◽

2003 ◽

Vol 9 (4) ◽

pp. 816-826

Author(s):

M. R. Yaghoobi Ershadi ◽

A. A. Akhavan ◽

A. V. Zahraei Ramazani ◽

M. R. Abai ◽

B. Ebrahimi ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Epidemiological Study ◽

Leishmania Major ◽

Reservoir Host ◽

Age Group ◽

Phlebotomus Papatasi ◽

Islamic Republic ◽

Islamic Republic Of Iran ◽

Rhombomys Opimus

An outbreak of cutaneous leishmaniasis [CL] in Sabzevar county prompted this study of the epidemiology and the ecology of vectors and reservoirs. Examination of 541 schoolchildren showed rates of 9.4% for scars and 5.9% for ulcers. Among 807 inhabitants of 4 villages, 10.4% had scars and 3.0% had active lesions. The most highly infected age group was 0-4 years with a rate of 5.9%. A total of 12 849 sandflies representing 7 species were collected in the study area. Leptomonad infection was found in Phlebotomus papatasi, P. caucasicus and Sergentomyia sintoni. Parasites from man, P. papatasi and Rhombomys opimus, were isolated and characterized as Leishmania major. Based on this survey, this is an epidemic of zoonotic CL, with R. opimus the main reservoir host, and P. papatasi the main vector

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Molecular characterization of Leishmania tropica and Leishmania major from stray dogs and patients in Saudi Arabia

10.21203/rs.2.22961/v1 ◽

2020 ◽

Author(s):

Abdullah D Alanazi ◽

Abdulazi S Alouffi S Alouffi ◽

Mohamed S Alyousif S Alyousif ◽

Abdulsadah A Rahi ◽

Magada A Ali ◽

...

Keyword(s):

Saudi Arabia ◽

Cutaneous Leishmaniasis ◽

Nested Pcr ◽

Leishmania Major ◽

Sand Fly ◽

Human Populations ◽

Leishmania Tropica ◽

Conventional Pcr ◽

Stray Dogs ◽

Control And Prevention

Abstract Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when occurring in sympatry in the same area, the role of each species in the epidemiology of cutaneous leishmaniasis is not clear.Methods: To determine the prevalence and to identify the species of Leishmania that infect humans and stray dogs in Riyadh and Al-Qaseem (Saudi Arabia), blood samples were collected from stray dogs (n = 311) and human patients (n = 27). A conventional PCR coupled with a nested PCR (n PCR) were applied in this study.Results: A conventional PCR coupled with a nested PCR (n PCR) showed that seven patients (25.9%) from Riyadh city and Al-Qaseem province were infected by L. major and L. tropica and five dogs (1.6%) by L. tropica.Conclusions: This is one of the first molecular studies of leishmaniasis from Saudi Arabia. The relationship between the sand fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and further epidemiological investigations of domestic and wild canine infected with L. major and L. tropica are needed towards a control and prevention of the infection in canine and human populations.

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High-resolution melting analysis identifies reservoir hosts of zoonotic Leishmania parasites in Tunisia

Parasites & Vectors ◽

10.1186/s13071-021-05138-x ◽

2022 ◽

Vol 15 (1) ◽

Author(s):

Moufida Derghal ◽

Abir Tebai ◽

Ghofrane Balti ◽

Hajer Souguir-Omrani ◽

Jomaa Chemkhi ◽

...

Keyword(s):

High Resolution ◽

Leishmania Major ◽

High Resolution Melting ◽

Reservoir Host ◽

Sand Fly ◽

Canine Leishmaniasis ◽

Multiple Infections ◽

Epidemiological Surveys ◽

Reservoir Hosts

Abstract Background Leishmaniasis is endemic in Tunisia and presents with different clinical forms, caused by the species Leishmania infantum, Leishmania major, and Leishmania tropica. The life cycle of Leishmania is complex and involves several phlebotomine sand fly vectors and mammalian reservoir hosts. The aim of this work is the development and evaluation of a high-resolution melting PCR (PCR-HRM) tool to detect and identify Leishmania parasites in wild and domestic hosts, constituting confirmed (dogs and Meriones rodents) or potential (hedgehogs) reservoirs in Tunisia. Methods Using in vitro-cultured Leishmania isolates, PCR-HRM reactions were developed targeting the 7SL RNA and HSP70 genes. Animals were captured or sampled in El Kef Governorate, North West Tunisia. DNA was extracted from the liver, spleen, kidney, and heart from hedgehogs (Atelerix algirus) (n = 3) and rodents (Meriones shawi) (n = 7) and from whole blood of dogs (n = 12) that did not present any symptoms of canine leishmaniasis. In total, 52 DNA samples were processed by PCR-HRM using both pairs of primers. Results The results showed melting curves enabling discrimination of the three Leishmania species present in Tunisia, and were further confirmed by Sanger sequencing. Application of PCR-HRM assays on reservoir host samples showed that overall among the examined samples, 45 were positive, while seven were negative, with no Leishmania infection. Meriones shawi were found infected with L. major, while dogs were infected with L. infantum. However, co-infections with L. major/L. infantum species were detected in four Meriones specimens and in all tested hedgehogs. In addition, multiple infections with the three Leishmania species were found in one hedgehog specimen. Sequence analyses of PCR-HRM products corroborated the Leishmania species found in analyzed samples. Conclusions The results of PCR-HRM assays applied to field specimens further support the possibility of hedgehogs as reservoir hosts of Leishmania. In addition, we showed their usefulness in the diagnosis of canine leishmaniasis, specifically in asymptomatic dogs, which will ensure a better evaluation of infection extent, thus improving elaboration of control programs. This PCR-HRM method is a robust and reliable tool for molecular detection and identification of Leishmania and can be easily implemented in epidemiological surveys in endemic regions. Graphical Abstract

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Assessing public perception of a sand fly biting study on the pathway to a controlled human infection model for cutaneous leishmaniasis

Research Involvement and Engagement ◽

10.1186/s40900-021-00277-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Vivak Parkash ◽

Georgina Jones ◽

Nina Martin ◽

Morgan Steigmann ◽

Elizabeth Greensted ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Study Design ◽

Public Involvement ◽

Human Infection ◽

Sand Fly ◽

Infection Model ◽

Sand Flies ◽

Link Type ◽

Stage Of Development ◽

Facing Material

Abstract Background A controlled human infection model (CHIM) involves deliberate exposure of volunteers to pathogens to assess their response to new therapies at an early stage of development. We show here how we used public involvement to help shape the design of a CHIM to support future testing of candidate vaccines for the neglected tropical disease cutaneous leishmaniasis, a disease transmitted by the bite of infected sand flies in tropical regions. Methods We undertook a public involvement (PI) consultation exercise to inform development of a study to test the safety and effectiveness of a sand fly biting protocol using uninfected sand flies (FLYBITE: ClinicalTrials.gov ID NCT03999970) and a CHIM using Leishmania major-infected sand flies (LEISH_Challenge: ClinicalTrials.gov ID NCT04512742), both taking place in York, UK. We involved 10 members of the public including a patient research ambassador and a previous CHIM volunteer. The session took place at The University of York, UK and examined draft study volunteer-facing material and included the CHIM study design, potential adverse events and therapeutic interventions at study endpoints. A discussion of the scientific, ethical, humanitarian and economic basis for the project was presented to the participants to provoke discourse. An inductive, thematic analysis was used to identify the participants’ key concerns. Results Themes were identified relating to i) quality of volunteer-facing written information, ii) improving study design, and iii) factors to motivate involvement in the research. Group participants responded positively to the overall study aims. Initial concerns were expressed about potential risks of study involvement, but further explanation of the science and mitigations of risk secured participant support. Participants provided advice and identified improved terminology to inform the volunteer-facing material. Lastly, treatment options were discussed, and excision of any cutaneous lesion was favoured over alternatives as a treatment. Conclusion The consultation exercise provided invaluable information which led to improved study design and enhanced clarity in the volunteer-facing material. The session also reinforced the need to maintain public trust in scientific rigour prior to initiation of any study. The investigators hope that this description strengthens understanding of PI in clinical research, and encourages its use within other studies.

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Risk Assessment of the Role of the Ecotones in the Transmission of Zoonotic Cutaneous Leishmaniasis in Central Tunisia

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18179274 ◽

2021 ◽

Vol 18 (17) ◽

pp. 9274

Author(s):

Walid Barhoumi ◽

Ifhem Chelbi ◽

Wasfi Fares ◽

Sami Zhioua ◽

Mohamed Abbas ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Leishmania Major ◽

Etiologic Agent ◽

Control Measures ◽

Sand Fly ◽

Main Peak ◽

Sand Flies ◽

Central Tunisia ◽

Zoonotic Cutaneous Leishmaniasis ◽

Significant Difference

Zoonotic cutaneous leishmaniasis (ZCL), endemic in Central and Southern Tunisia, is caused by Leishmania major (Kinetoplastida: Trypanosomatidae), which is transmitted by the sand fly Phlebotomus papatasi. In Tunisia, the fat sand rat Psammomys obesus and the desert jird Meriones shawi are the principal reservoir hosts of L. major. The presence of the P. papatasi vector of the L. major etiologic agent of ZCL was assessed in the vicinity of villages in endemic areas of Central Tunisia. The study was performed from September through October 2019, a period corresponding to the main peak of activity of P. papatasi. Sand flies were collected from rodent burrows located at the ecotone level, which is the transition zone between the natural environment and human settlement. Sand flies were identified to species level and tested for the presence of L. major by PCR. Our entomological survey showed that P. papatasi is the most abundant sand fly species associated with rodent burrows, and this abundance is even higher in ecotones primarily occupied by P. obesus in comparison to ecotones occupied by M. shawi. Infections with Leishmania major were detected only in P. papatasi, with an overall minimum infection rate (MIR) of 2.64%. No significant difference was observed between the MIRs in ecotones of P. obesus and of M. shawi. Incidence of ZCL in the studied areas ranged from 200 to 700 cases per 100,000 inhabitants, with a mean incidence of 385.41 per 100,000. Higher ZCL incidence was identified in ecotones of M. shawi compared to ecotones of P. obesus. ZCL cases are positively correlated with the MIRs. Considering the short flight range of P. papatasi, increases in its densities associated with burrows of P. obesus or M. shawi at the ecotone level expand the overlap of infected vectors with communities and subsequently increase ZCL incidence. Therefore, control measures should target P. papatasi populations at the ecotones.

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Molecular Characterisation of Leishmania Species from Stray Dogs and Patients in Saudi Arabia

10.21203/rs.3.rs-133336/v1 ◽

2020 ◽

Author(s):

Abdullah D Alanazi ◽

Abdulazi S Alouffi ◽

Mohamed S Alyousif ◽

Abdulsadah A Rahi ◽

Magda A Ali ◽

...

Keyword(s):

Saudi Arabia ◽

Cutaneous Leishmaniasis ◽

Leishmania Major ◽

Leishmania Species ◽

Sand Fly ◽

Human Populations ◽

Nested Polymerase Chain Reaction ◽

Stray Dogs ◽

Control And Prevention

Abstract Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when they occur in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. Methods: To determine the frequency of occurrence and to identify the species of Leishmania that infect humans and stray dogs in Riyadh and Al-Qaseem (Saudi Arabia), 311 stray dogs and 27 human patients who were suspected for Leishmania were examined for CL by a nested polymerase chain reaction (nPCR).Results: The use of nPCR detected seven patients (25.9%) who were positive for cutaneous leishmaniasis. Five patients from Riyadh were infected by L. major and two from Al-Qaseem by L. tropica. In addition, five dogs (1.6%) were infected by L. tropica. Conclusions: This is one of the first molecular studies of leishmaniasis to be conducted in Saudi Arabia. The relationship between the sand-fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and epidemiological investigations are required in order to progress towards control and prevention of the infection in canine and human populations.

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A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study)

Wellcome Open Research ◽

10.12688/wellcomeopenres.16870.1 ◽

2021 ◽

Vol 6 ◽

pp. 168

Author(s):

Vivak Parkash ◽

Helen Ashwin ◽

Jovana Sadlova ◽

Barbora Vojtkova ◽

Georgina Jones ◽

...

Keyword(s):

Focus Groups ◽

Leishmania Major ◽

Human Infection ◽

Sand Fly ◽

Infection Model ◽

Sand Flies ◽

Serious Adverse Events ◽

Natural Sand ◽

Early Evaluation ◽

Significant Difference

Background: Leishmaniasis is a globally important yet neglected parasitic disease transmitted by phlebotomine sand flies. With new candidate vaccines in or near the clinic, a controlled human challenge model (CHIM) using natural sand fly challenge would provide a method for early evaluation of prophylactic efficacy. Methods: We evaluated the biting frequency and adverse effects resulting from exposure of human volunteers to bites of either Phlebotomus papatasi or P. duboscqi, two natural vectors of Leishmania major. 12 healthy participants were recruited (mean age 40.2 ± 11.8 years) with no history of significant travel to regions where L. major-transmitting sand flies are prevalent. Participants were assigned to either vector by 1:1 allocation and exposed to five female sand flies for 30 minutes in a custom biting chamber. Bite frequency was recorded to confirm a bloodmeal was taken. Participant responses and safety outcomes were monitored using a visual analogue scale (VAS), clinical examination, and blood biochemistry. Focus groups were subsequently conducted to explore participant acceptability. Results: All participants had at least one successful sand fly bite with none reporting any serious adverse events, with median VAS scores of 0-1/10 out to day 21 post-sand fly bite. Corresponding assessment of sand flies confirmed that for each participant at least 1/5 sand flies had successfully taken a bloodmeal (overall mean 3.67±1.03 bites per participant). There was no significant difference between P. papatasi and P. duboscqi in the number of bites resulting from 5 sand flies applied to human participants (3.3±0.81 vs 3.00±1.27 bites per participant; p=0.56). In the two focus groups (n=5 per group), themes relating to positive participant-reported experiences of being bitten and the overall study, were identified. Conclusions: These results validate a protocol for achieving successful sand fly bites in humans that is safe, well-tolerated and acceptable for participants. Clinicaltrials.gov registration: NCT03999970 (27/06/2019)

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